Three members of the GATA family of zinc finger transcription factors, GATA-4, -5, and -6, are expressed within cardiac and smooth muscle cells in the developing cardiovascular system and have been shown to bind essential regulatory elements in the control regions of cardiac-specific genes. However, little is known of the regulatory factors that control GATA gene expression or of the mechanisms whereby GATA factors activate gene expression in developing cardiac or smooth muscle cells. The overall goal of this project is to define the functions of GATA factors during heart development and disease. Mice bearing null mutations in each of the GATA genes singly and in combination will be analyzed for cardiogenic defects. The regulatory elements that confer cardiac specificity to the GATA4 and -6 genes will also be identified and used to define the transcription factors that initiate cardiogenesis. The potential involvement of several GATA-interacting proteins in the control of cardiac gene expression will also be investigated. These studies will lead to a comprehensive understanding of the unique and potentially overlapping functions of GATA4, -5, and -6 during cardiovascular development and will provide insights into the transcriptional networks involved in normal and abnormal development of the cardiovascular system.